Development of a Bio-tissue Oxygenation Nanophosphor Enabled Sensing (BONES) system for Quantifying Hypoxia in Bone Marrow

项目摘要/摘要 众所周知，低氧(低氧)环境对维持小的 人体内成体干细胞的数量，如在骨髓中。这些条件是 也被认为能使处于休眠状态的癌细胞在几年或几十年后存活和转移 原来的肿瘤已经被摧毁了，为什么骨髓是最多的 常见的癌症转移部位。对这些情况的了解可以推动 开发用于体外培养干细胞的3D细胞支架，从而减轻 需要骨髓移植，以及开发防止癌症复发的治疗方法。 该项目计划开发第一个定量氧气断层成像系统。 称为骨骼(生物组织氧合纳米磷支持的传感)以解决关键的 需要对低氧(低氧)组织中的氧浓度进行高分辨率成像 作为骨髓。这项技术是基于x射线发光计算的发展 层析成像--一种能够达到细胞水平的新兴分子成像技术 分辨率高、灵敏度高。这种方法使用x射线来刺激氧气敏感。 发射近红外光子的纳米磷光体最终能够实现3D氧气测量 深厚的骨髓。 因为这项技术需要一个拥有x射线专业知识的多学科团队，纳米荧光粉 专门知识、近红外探测专业知识和量化浓度的算法 并将剂量降至最低，这项STTR快速通道提案涉及几个机构，这些机构 在各自领域的专业知识。拟议的第一阶段为期6个月的项目是- 用于低氧纳米荧光粉的面包板系统的原理论证 解决方案并嵌入到骨骼中。拟议的第二期为期24个月的项目是开发一个 完成了原型系统并对其性能进行了实验验证。

Project Summary/Abstract Low oxygen (hypoxic) environments are known to be important for maintaining the small number of adult stem cells in the human body, such as in bone marrow. These conditions are also believed to enable dormant cancer cells to survive and metastasize years or decades after the original tumor has been destroyed and the reason why bone marrow is one of the most common sites of cancer metastasis. Understanding of these conditions can drive the development of 3D cellular scaffolds for growing stem cells ex vivo, thus reducing the burden on requiring bone marrow transplants, and for developing therapeutics that prevent cancer relapse. This project proposes to develop the first quantitative oxygen tomographic imaging system called BONES (Bio-tissue Oxygenation Nanophosphor Enabled Sensing) to address the critical need for high resolution imaging of oxygen concentrations in hypoxic (low oxygen) tissues such as bone marrow. The technique is based on developments in x-ray luminescence computed tomography, an emerging molecular imaging technique capable of achieving cellular level resolution and high sensitivities. The approach uses x-rays to excite oxygen-sensitive nanophosphors that emit near-infrared photons to finally enable 3D oxygen measurements in deep bone marrow. Because the technique requires a multidisciplinary team with x-ray expertise, nanophosphor expertise, near-infrared detection expertise, and algorithms for quantifying the concentrations and minimizing dose, this STTR fast-track proposal involves several institutions with deep expertise in their respective domains. The proposed Phase I 6-month project is a proof-of- principle demonstration of a breadboard system used on nanophosphors in low oxygen solutions and embedded in bone. The proposed Phase II 24-month project is to develop a complete prototype system and experimentally verify its performance.